HHT genes and phenotypic associations. (A) Endothelial vasculopathy genes and variants identified in current study cohort. Note that the major HHT genes are ACVRL1 (red) and ENG (green).^6-8 SMAD4^6,9  is less common, and GDF2 was more recently described as HHT causal,⁴⁴  whereas EPHB4 and RASA1 cause separate endothelial vasculopathies (CM-AVM2 and CM-AVM1) that overlap phenotypically with HHT. (B) Schematic of the cohort of 104 patients plotted on 4 separate axes for hemorrhage (H), anemia (A), thrombosis (T), and deep-seated infection (I). Ten deep-seated infections were in association with concurrent and presumed causative pulmonary AVMs (cerebral and spinal abscesses, spinal discitis, and septic arthritis due to polymicrobial flora, particularly anaerobic and aerobic commensals of the gastrointestinal and periodontal spaces^31-33 ). Blue numbers indicate the number of the cohort with no events/no excess (H₀, A₀, T₀, and I₀), precipitated events (H₁, A₁, T₁), and spontaneous events (H₂, A₂, T₂, and I₁). I₁ were cerebral abscess (N = 6), spinal discitis (N = 2), spinal abscess (N = 1), septic arthritis (N = 1), recurrent bacterial endocarditis (N = 1), osteomyelitis (N = 1), and recurrent sepsis (N = 1). (C) Violin plots for ACVRL1 (left, red) and ENG (right, green) patients orientated on the 3 axes as in (B).